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Natalie C DuPre, Richard Flavin, Karen S Sfanos, Robert H Unger, Samantha To, Elizaveta Gazeeva, Michelangelo Fiorentino, Angelo M De Marzo, Jennifer R Rider, Lorelei A Mucci
BACKGROUND: Corpora amylacea are amyloid bodies commonly found adjacent to damaged prostate epithelium. Little is known about their formation or function. The current study sought to characterize corpora amylacea in prostate tissue and to describe their relationship with clinical, histological, molecular, and lifestyle factors, especially with chronic inflammation which is associated with aggressive disease. METHODS: We studied a cohort of 355 men with prostate cancer and tissue specimens from the Health Professionals Follow-Up Study...
July 15, 2018: Prostate
Tiejun Yang, Yifeng Jing, Jun Dong, Xinpei Yu, Mingming Zhong, Laura E Pascal, Dan Wang, Zhongxian Zhang, Baoping Qiao, Zhou Wang
BACKGROUND: Elongation factor for RNA polymerase 2 (ELL2) and ELL associated factor 2 (EAF2) have been reported to have tumor suppressive properties in prostate epithelial cells. AIMS: We investigated ELL2 expression in human prostate cancer specimens, and ELL2 protein stability and ubiquitination in prostate cancer cells. MATERIALS AND METHODS: Immunostaining analysis of human prostate cancer specimens was used to determine ELL2 expression in tumor and normal tissues...
July 15, 2018: Prostate
Wenjing He, Junhe Li
BACKGROUND: Exendin-4, one of the most widely used antidiabetic drugs, has recently been reported to have potential antitumor effects in cancers. Prostate cancer (PC) is one of the most common cancers in male patients with type 2 diabetes mellitus, and radiotherapy plays a vital role in the therapy of PC. Whether exendin-4 has the potential to enhance PC response to ionizing radiation (IR) remains unknown. We aimed to explore whether exendin-4 radiosensitizes PC cells. METHODS: GLP-1 receptor (GLP-1R) expression in PC tissue samples and cell lines were analyzed, Human prostate cancer cells (PC3 and LNCap) were treated with IR and exendin-4, and subjected to proliferation, clone formation, cell cycle, immunoblotting, and immunohistochemical analysis...
July 15, 2018: Prostate
Dawei Li, Guimei Tian, Jia Wang, Lisa Y Zhao, Olivia Co, Zoe C Underill, Joe S Mymryk, Frank Claessens, Scott M Dehm, Yehia Daaka, Daiqing Liao
BACKGROUND: Mutations or truncation of the ligand-binding domain (LBD) of androgen receptor (AR) underlie treatment resistance for prostate cancer (PCa). Thus, targeting the AR N-terminal domain (NTD) could overcome such resistance. METHODS: Luciferase reporter assays after transient transfection of various DNA constructs were used to assess effects of E1A proteins on AR-mediated transcription. Immunofluorescence microscopy and subcellular fractionation were applied to assess intracellular protein localization...
July 15, 2018: Prostate
Maki Kurita, Hiroshi Yamaguchi, Ken Okamoto, Takashi Kotera, Michiko Oka
BACKGROUND: Experimental autoimmune prostatitis (EAP) is most often used as a nonbacterial model of chronic prostatitis/chronic pelvic pain. We investigated the development of chronic pelvic pain and inflammatory changes in rat EAP and examined the effect of a single treatment with phosphodiesterase 5 (PDE5) inhibitors on the chronic pelvic pain. METHODS: EAP was induced in rats by intradermal injection of rat prostate antigen and complete Freund's adjuvant on days 0 and 28...
July 15, 2018: Prostate
Thambi Dorai, Ankeeta Shah, Faith Summers, Rajamma Mathew, Jing Huang, Tze-Chen Hsieh, Joseph M Wu
In the course of studies aimed at the role of oxidative stress in the development of metastatic potential in the LNCaP-C4-2B prostate cancer progression model system, we found a relative decrease in the level of expression of the cytoplasmic nicotinamide riboside: quinone oxidoreductase (NQO2) and an increase in the oxidative stress in C4-2B cells compared to that in LNCaP or its derivatives C4 and C4-2. It was also found that C4-2B cells specifically shed large extracellular vesicles (LEVs) suggesting that these LEVs and their cargo could participate in the establishment of the osseous metastases...
July 15, 2018: Prostate
Michael F Tweedle, Haiming Ding, William T Drost, Joshua Dowell, James Spain, Mathew Joseph, Said M Elshafae, Maria-Isabela Menendez, Li Gong, Shankaran Kothandaraman, Wessel P Dirksen, Chadwick L Wright, Robert Bahnson, Michael V Knopp, Thomas J Rosol
BACKGROUND: Ace-1 canine prostate cancer cells grow orthotopically in cyclosporine immunosuppressed laboratory beagles. We previously transfected (human Gastrin-Releasing Peptide Receptor, huGRPr) into Ace-1 cells and demonstrated receptor-targeted NIRF imaging with IR800-G-Abz4-t-BBN, an agonist to huGRPr. Herein, we used the new cell line to develop the first canine prostate cancer model expressing a human growth factor receptor. METHODS: Dogs were immunosuppressed with cyclosporine, azathioprine, prednisolone, and methylprednisolone...
July 11, 2018: Prostate
Caroline Bsirini, Alexandra M Danakas, Hiroshi Miyamoto
BACKGROUND: No consensus has been reached for an optimal method of quantifying discontinuous tumor foci separated by intervening benign tissue on prostate biopsy (PBx). We examined sets of PBx, where cancer involved only one core, and corresponding radical prostatectomy (RP) specimens. METHODS AND RESULTS: Cases were divided into 3 groups-Group 1 (n = 80): <3 mm in end-to-end tumor measurement (continuous/discontinuous); Group 2 (n = 22): ≥3 mm in tumor length (continuous); and Group 3 (n = 15): ≥3 mm in end-to-end tumor measurement (discontinuous)...
July 11, 2018: Prostate
Daniel M Lim, Roman Gulati, Serge Aleshin-Guendel, Agnes Gawne, Jonathan T Wingate, Heather H Cheng, Ruth Etzioni, Evan Y Yu
BACKGROUND: Optimal utilization of novel therapies for advanced prostate cancer is challenging without a validated surrogate efficacy endpoint. Ongoing trials are using durable undetectable prostate-specific antigen (PSA) levels as a marker of efficacy. The clinical relevance of prolonged undetectable PSA after a short course of androgen deprivation therapy (ADT) is uncertain. METHODS: The University of Washington Caisis database was queried for radical prostatectomy patients who received 6-12 months of ADT after biochemical recurrence (BCR), defined as PSA ≥0...
July 10, 2018: Prostate
Ryan Butel, Richard Ball
BACKGROUND: We observed in cystoprostatectomy specimens that Bacillus Calmette-Guérin (BCG) granulomatous prostatitis tended preferentially to affect the peripheral zone (PZ) and aimed to study the matter, postulating that assessment of its distribution might contribute to understanding pathogenetic processes. METHODS: Entire prostate glands from 27 men (47-83 years; mean = 69 years), who had previously received intravesical BCG therapy for non-muscle-invasive urothelial carcinoma of the bladder, were studied as whole-mount sections to determine the anatomical distribution and histopathological characteristics of BCG prostatitis...
July 10, 2018: Prostate
Julian M Rogasch, Hannes Cash, Sebastian Zschaeck, Sefer Elezkurtaj, Winfried Brenner, Bernd Hamm, Marcus Makowski, Holger Amthauer, Christian Furth, Alexander D J Baur
PURPOSE: To evaluate the accuracy of clinical parameters and established pre-treatment risk stratification systems for prostate cancer (PCa) in predicting PSMA-positive metastases in men undergoing Ga-68-PSMA PET/CT as initial staging examination. MATERIALS AND METHODS: A retrospective analysis in 108 consecutive treatment-naïve patients with biopsy-proven PCa undergoing Ga-68-PSMA PET/CT (median age, 72 years [range, 49-82 years]) was performed. Prediction of PSMA-positive metastases by serum PSA, clinical T stage (cT), ISUP group, percentage of positive biopsy cores, and derived risk scores (D'Amico risk classification system, Roach [RF], Yale formula [YF], and Briganti nomogram [BN]) was examined with ROC analysis...
July 5, 2018: Prostate
Shanshan Zhao, Amy Leonardson, Milan S Geybels, Andrew S McDaniel, Ming Yu, Suzanne Kolb, Hong Zong, Kelly Carter, Javed Siddiqui, Anqi Cheng, Jonathan L Wright, Colin C Pritchard, Raymond Lance, Dean Troyer, Jian-Bing Fan, Elaine A Ostrander, James Y Dai, Scott A Tomlins, Ziding Feng, Janet L Stanford
BACKGROUND: Prognostic biomarkers for localized prostate cancer (PCa) could improve personalized medicine. Our group previously identified a panel of differentially methylated CpGs in primary tumor tissue that predict disease aggressiveness, and here we further validate these biomarkers. METHODS: Pyrosequencing was used to assess CpG methylation of eight biomarkers previously identified using the HumanMethylation450 array; CpGs with strongly correlated (r >0...
June 28, 2018: Prostate
Jin-Chun Lu, Jia-Ming Shen, Xue-Chun Hu, Long-Ping Peng, Zhi-Wei Hong, Bing Yao
BACKGROUND: Experimental models have confirmed that autoimmunity is an important factor in the onset of chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS); however, there is no conclusive evidence on whether autoimmune prostatitis exists in human males. METHODS: Rabbits were immunized with either human prostate tissue homogenates or normal saline and the antiserum was collected. Two-dimensional electrophoresis (2-DE) was performed on the homogenates and Western blotting was conducted on the sera...
June 26, 2018: Prostate
Sarah F Cook, Michael V Fiandalo, David S Watt, Yue Wu, James L Mohler, Robert R Bies
BACKGROUND: Progression of castration-recurrent/resistant prostate cancer (CRPC) relies in part on dihydrotestosterone derived from intratumoral androgen metabolism. Mathematical modeling provides a valuable tool for studies of androgen metabolism in CRPC. This modeling approach integrates existing knowledge about complex biologic systems and provides a means of interrogating the effects of various interventions. We sought to model a single reaction in the androgen biosynthesis network, namely the oxidation of androsterone (AND) to androstanedione (5α-dione) by four 3α-oxidoreductase enzymes, as an initial effort to establish the feasibility of our modeling approach...
June 25, 2018: Prostate
Brian T Helfand, Haitao Chen, Richard J Fantus, Carly A Conran, Charles B Brendler, Siquan Lilly Zheng, Patrick C Walsh, William B Isaacs, Jianfeng Xu
PURPOSE: Family history assigns equivalent risk to all relatives based upon the degree of relationship. Recent genetic studies have identified single nucleotide polymorphisms (SNPs) that can be used to calculate a genetic risk score (GRS) to determine prostate cancer (PCa) risk. We sought to determine whether GRS can stratify PCa risk among individuals in families considered to be at higher risk due their family history of PCa. MATERIALS AND METHODS: Family members with hereditary PCa were recruited and genotyped for 17 SNPs associated with PCa...
June 19, 2018: Prostate
Pedro Barata, Hamid Emamekhoo, Prateek Mendiratta, Vadim Koshkin, Allison Tyler, Moshe Ornstein, Brian I Rini, Timothy Gilligan, Christos Kyriakopoulos, Jorge A Garcia
BACKGROUND: Androgen deprivation therapy plus docetaxel (D-ADT) increases overall survival (OS) in men with high-volume, metastatic hormone-sensitive prostate cancer (mHSPC). Although the vast majority of men initially respond to D-ADT, most will progress and develop castration-resistant prostate cancer (CRPC). Little is known about the optimal treatment sequence for men with progressive disease on D-ADT. PATIENT AND METHODS: Retrospective analysis of consecutive mHSPC patients treated with ≥3 cycles of D-ADT at Cleveland Clinic and University of Wisconsin-Madison was undertaken...
June 7, 2018: Prostate
Atish D Choudhury, Kathryn P Gray, Jeffrey G Supko, Lauren C Harshman, Mary-Ellen Taplin, Amanda F Pace, Matthew Farina, Katherine A Zukotynski, Brandon Bernard, Philip W Kantoff, Mark Pomerantz, Christopher Sweeney
BACKGROUND: Cabozantinib can enhance the effect of abiraterone in preclinical prostate cancer models. This study aimed to define the recommended phase 2 dose (RP2D) and preliminary efficacy of abiraterone + cabozantinib in mCRPC. METHODS: Patients with progressive mCRPC with 0-2 prior chemotherapy regimens but no prior CYP17A1 or MET inhibitor received abiraterone acetate at 1000 mg daily with prednisone 5 mg BID in combination with cabozantinib at 20, 40, or 60 mg daily in a dose-escalation 3 + 3 open-label phase 1 design (Part A)...
June 7, 2018: Prostate
Masaki Shiota, Naohiro Fujimoto, Katuyoshi Higashijima, Kenjiro Imada, Eiji Kashiwagi, Ario Takeuchi, Junichi Inokuchi, Katsunori Tatsugami, Shunichi Kajioka, Takeshi Uchiumi, Masatoshi Eto
BACKGROUND: Corticosteroids play important roles in prostate cancer therapeutics. However, their role when combined with enzalutamide remains obscure. Then, we aimed to elucidate the functional and clinical impact of corticosteroids on steroid receptors in androgen receptor (AR)-targeting therapy utilizing enzalutamide. METHODS: The therapeutic effect was studied according to concomitant use of corticosteroids in 86 men treated with enzalutamide. The sensitivity to various agents was evaluated using cytotoxicity assays in prostate cancer cells...
May 30, 2018: Prostate
Mark C Markowski, Gretchen K Hubbard, Jessica L Hicks, Qizhi Zheng, Alexia King, David Esopi, Apurv Rege, Srinivasan Yegnasubramanian, Charles J Bieberich, Angelo M De Marzo
BACKGROUND: Loss or mutation of PTEN alleles at 10q23 in combination with 8q24 amplification (encompassing MYC) are common findings in aggressive, human prostate cancer. Our group recently developed a transgenic murine model of prostate cancer involving prostate-specific Pten deletion and forced expression of MYC under the control of the Hoxb13 promoter. MYC overexpression cooperated with Pten loss to recapitulate lethal, human prostate cancer. METHOD: We now report on the generation of two mouse prostate cancer cell lines, BMPC1 and BMPC2, derived from a lymph node, and liver metastasis, respectively...
May 30, 2018: Prostate
Paige M Glumac, Colleen L Forster, Hong Zhou, Paari Murugan, Shilpa Gupta, Aaron M LeBeau
BACKGROUND: The transmembrane glycoprotein CD133 is believed to be a marker of adult prostate stem cells and cancer stem/initiating cells. Investigating the role of CD133 in the normal biology of the prostate and in cancer is complicated by the lack of a sensitive and accurate antibody for its detection. Here, we describe the characterization of a unique antibody identified using human antibody phage display that can recognize CD133 in both formalin-fixed tissues and cell lines. METHODS: A human single-chain variable fragment (scFv) antibody phage display library possessing a diversity of 8 × 109 was screened against fully glycosylated recombinant CD133...
May 22, 2018: Prostate
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